Numerous compounds and medicaments able to act at particular (different) points in the biochemical process associated with the respective pathological state have been disclosed for the treatment of diseases such as diabetes or Alzheimer's. To date, only a few compounds able to bring about an inhibition of the enzyme glycogen synthase kinase -3β(GSK-3β) have been disclosed for the treatment of metabolic disorders.
Thus, WO 04/046117 discloses pyridazinone derivatives suitable for inhibiting GSK-3β. The pyridazinone derivatives described therein differ from the compounds of the present invention in that, in place of a benzimidazole residue (or a derivative thereof), they have an amide substituent in position 4 of the pyridazinone which can be linked both via the amide carbon atom and via the amide nitrogen atom to the basic pyridazinone structure.
In addition, numerous pyridazinone derivatives are described in the literature but differ from the compounds of the invention through a different substitution pattern and (in some cases) different indications. Thus, it is possible from the general formula disclosed in WO 01/74786 to derive pyridazinone derivatives which, although they may have a benzimidazole substituent in position 4, on the other hand they have a sulfonamide group in position 5, in contrast to the compounds of the present invention. The compounds described in WO 01/74786 have an inhibitory effect on phosphodiesterase-7 and can be used in the treatment of autoimmune diseases.
JP-A 09 216883 discloses pyridazinone derivatives which can be used for the treatment of heart failure or high blood pressure. The pyridazinone derivatives described therein have in position 6 a pyrazolo[1,5-a]pyridine substituent which is in turn substituted in position 2 by aryl, preferably phenyl. The pyridazinone ring itself is additionally substituted in position 2 by substituents such as hydrogen, lower alkyl or a heterocycle, while position 4 has substituents such as hydrogen, acyl, cyano, heterocyclyl, amino or a protected amino group. If the substituent in position 4 is a heterocycle, this preferably has 3 to 8 ring members and is saturated. A heterocyclic group is not, however, among the preferred substituents in position 4 of the pyridazinone ring of the compounds disclosed and claimed in this document.
Compounds explicitly disclosed in JP-A 09 216883 are not an aspect of the present invention.
WO 03/059891 by contrast discloses pyridazinone derivatives which can be used to treat diseases which are caused or intensified by unregulated p38 MAP kinase and/or TNF activity. The compounds described therein are suitable for example for the treatment of inflammations, of diabetes, of Alzheimer's disease or of cancer. They differ from the compounds of the invention in that the nitrogen in position 2 is mainly substituted by alkyl, aryl or heteroaryl and in that a heteroaryl substituent such as benzimidazole is not defined for position 4 of the pyridazinone.
Bicyclic heterocycles having an aggregation inhibiting effect are described in EP-A 0 639 575. It is possible from the general formula (I) specified therein to derive for the bicyclic system having substituent a benzimidazole derivative which must have at least one further ring nitrogen atom. It is additionally possible to derive for the substituent B theoretically a pyridazinone derivative which in turn must obligatorily be provided with a multi-membered substituent which obligatorily comprises a 1,4-cyclohexylene or 1,4-cyclohex-3-enylene group and a carbonyl group. It is thus evident that the compounds of the invention are not disclosed by EP-A 0 639 575 and compounds explicitly disclosed by EP-A 0 639 575 are not an aspect of the present invention However, all of the documents discussed above are hereby incorporated by reference.
The compounds of general formula (I) are kinase inhibitors and can therefore be employed for the treatment of diseases, which may result from an abnormal activity of kinases. Abnormal kinase activity, may also be found in for example, that of PI3K, AkT, GSK-3β kinase enzyme